Alveolar rhabdomyosarcoma is a soft tissue tumor which occurs in the pediatric population. Because of its aggressive behavior and associated poor prognosis, it is clinically important to distinguish this tumor from the embryonal subtype of rhabdomyosarcoma as well as other pediatric neoplasms. However, histologic diagnosis is often complicated by the paucity of features of striated muscle differentiation and its similarity to a large group of pediatric solid tumors that can present as collections of poorly differentiated small, round cells.
The course of action to be taken in a patient exhibiting small, round cell tumors is difficult to select because each tumor type in this category has its own treatment regimen. Patients suffering from alveolar rhabdomyosarcoma must be treated with surgery and a relatively potent and specific chemotherapy regimen. Because the determination of whether a tumor is alveolar rhabdomyosarcoma or not suggests the prognosis and what course of treatment is warranted, it is crucial to be able to identify whether or not a tumor is alveolar rhabdomyosarcoma in a fast, efficient and reliable manner.
If a tumor is diagnosed as being alveolar rhabdomyosarcoma, aggressive treatment for patients suffering from such tumors is undertaken to destroy and/or remove it.
After surgery is performed, there is a need to determine whether or not the surgeon removing the tumor has removed a sufficiently large section of tissue to ensure that no malignant cells remain. Normally, tissue from the margin of surgical resection is obtained and analyzed by a pathologist who examines the material to detect alveolar rhabdomyosarcoma cells. There are shortcomings to these procedures; in particular, it is very possible that tumor cells which are present can escape detection.
In addition to examining surrounding tissue to determine if metastasis has taken place, it is also desirable to test bone marrow. Using the currently available techniques, such examinations are insufficiently sensitive in many cases.
Moreover, early detection of reoccurring tumors is desirable in order to indicate the need to begin therapy again. It is desirable to be able to detect cells at the earliest possible time.
Cytogenetic investigations have recently identified a characteristic translocation of chromosome 2 and 13 t(2;13)(q35;q14) in the majority of alveolar rhabdomyosarcomas (Douglass, E. C. et al., (1987) Cytogenetics and Cell Genetics 45:148-155). That is, a portion of chromosome 2 and a port of chromosome 13 each break off from their respective chromosomes and attach to the other chromosome. Thus, in the alveolar rhabdomyosarcoma cells, the derivative chromosome 2 contains a portion of chromosome 13 and the derivative chromosome 13 contains a portion of chromosome 2.
The association of alveolar rhabdomyosarcoma with a specific chromosomal translocation permits alveolar rhabdomyosarcoma cells to be distinguished from other small, round tumor cells by microscopic examination of genetic material from tumor cells. Metaphase chromosomes must be observed and abnormalities detected. Karyotypes are made using the chromosomes from tumor cells. Chromosomes 2 and 13 are visually inspected to discover whether or not translocation has occurred. This procedure has several shortcomings. It is time consuming and relies on unpredictable growth and chromosomal banding characteristics of the tumor cells. Moreover, it requires a high degree of expertise and often repeated attempts.
Accordingly, there is a need for an improved method of detecting the presence of alveolar rhabdomyosarcoma tumor cells.